Osteoporosis is a bone disease characterized by low bone mass and structural deterioration of bone tissue, leading to increased bone fragility and susceptibility to fracture, especially in the spine, hip and wrist areas. Osteoporosis is a major public health and economic problem. According to the US National Osteoporosis Foundation, osteoporosis affects about 44million Americans. It is estimated that 10 million individuals in the U.S. already have the disease and almost 34 million more are estimated to have low bone mass, placing them at increased risk for osteoporosis. Approximately 80% of those affected by osteoporosis are women. Data indicates that one out of every two women and one in four men over 50 will have an osteoporosis related fracture in their lifetime. However, osteoporosis can strike at any age. Osteoporosis is responsible for more than 1.5 million fractures annually. The estimated national direct expenditures (hospitals and nursing homes) for osteoporosis and related fractures total about $14 billion each year.
Osteoporosis and/or other related bone diseases lower a patient's quality of life, making the prevention and/or treatment of the diseases an important subject matter. Many alternatives are available to prevent and/or treat osteoporosis such as: Estrogen/Hormone Replacement Therapy (ERT/HRT) commercially available under the name Estrace®, Estraderm®, Premarin® etc.; Selective Estrogen Receptor Modulators (SERMs) commercially available under the name Evista®; bisphosphonates commercially available under the name Fosamax®, Boniva®, Actonel® etc. Other medications are also available such as calcitonin commercially available under the name Miacalcin®; calcium supplements; vitamin D; and sodium fluoride.
Bisphosphonates appear to be one of the most effective and popular options for the prevention and/or treatment of osteoporosis and other related diseases such as Paget's disease, malignant hypercalcemia and metastatic bone disease, etc. Currently marketed bisphosphonates are available for oral or intravenous administration. Oral administration is generally favorable due to its ease of administration. However, oral administration of bisphosphonates is associated with low bioavailability and is also known to cause gastrointestinal related side effects including: esophagitis, esophageal ulceration, retrosternal pain, and local irritation of the upper gastrointestinal mucosa. In addition, administration of bisphosphonates involves complicated and inconvenient procedures. Under the best conditions, oral bioavailability of bisphosphonates like Fosamax®, Boniva® and Actonel® is less than 1%, and bioavailability is even less if the recommendations for administration are not followed. It is estimated that only about 50% of orally absorbed bisphosphonates reach the therapeutic sites, while the rest is excreted in the urine.
Intravenous (“IV”) administration of bisphosphonates is common for the treatment of hypercalcemia but is not the normal method of administration for the treatment of osteoporosis. Furthermore, IV administration of bisphosphonates involves complicated and inconvenient administration procedures and is associated with more adverse effects, such as osteonecrosis of the Jaw (“ONJ”). It has been reported that 97% of ONJ related to bisphosphonate drugs were affiliated with IV administration. In either administration, the drug reaches its peak in a short period of time and is cleared out of the system within a couple of hours.
Due to their poor bioavailability, bisphosphonate drugs need to be continuously administered for years to be effective in the prevention/treatment of osteoporosis. However, due to their inconvenient administration requirements and associated side effects, their application for long term prevention and treatment in patients with osteoporosis is challenging and limited.